Juvenile Xanthogranuloma of the Head and Neck: Imaging Findings in 11 Cases.

BACKGROUND: Juvenile Xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, occurring mainly in infancy. With an extracutaneous lesion, its diagnosis is difficult, because of a wide clinical spectrum. Here we demonstrate and characterize imaging features of 11 patients with JXG of the head and neck in various locations. MATERIAL AND METHODS: We recorded clinical data and reviewed all imaging studies of 11 patients with JXG of the head and neck. Ultrasonography (US) alone was performed in 1 patient; MRI alone in 6 patients; US and MRI in 1 patient; and US, CT, and MRI in 3 patients. We evaluated the following characteristics in all studies: location and number of lesions, echogenicity and vascularization on US, density on CT, signal intensity on T 1 - and T 2 -weighted images, ADC and enhancement on MRI, and tumor boundaries and bone involvement. RESULTS: Lesions were well-defined in 9 cases, and bone erosion was present in 2. On US, lesions were hypoechoic or hyperechoic and with or without vascularization. On CT, lesions were hyper-dense, with no calcification. On MRI, lesions were mildly hyper-intense or iso-intense on T 1 -weighted images in 8 of 9 patients, hypo-intense on T2-weighted images in 7 of 10, low ADC in 7 of 9, and enhancement in 7 of 7. CONCLUSIONS: The diagnosis of extra cutaneous JXG may be proposed, with the following suggestive criteria: age < 1 year, well-defined lesion, mild hyper-intensity on T 1 -weighted images, hypo-intensity on T 2 -weighted images, low ADC, enhancement, and possible adjacent bone involvement.

Congenital isolated juvenile xanthogranuloma of the sole - a unique case report in a newborn.

Juvenile xanthogranuloma (JXG) is a rare, benign non-Langerhans cell histiocytosis that primarily affects the skin, with infrequent extracutaneous manifestations. Lesions typically emerge during early childhood and often resolve spontaneously, obviating the need for treatment. This paper details the case of a child diagnosed with a solitary JXG on the sole, necessitating surgical excision due to its functional impairment, specifically a delay in walking and weight bearing.

Multiple juvenile xanthogranuloma.

Juvenile xanthogranuloma is the most frequent form of non-Langerhans cell histiocytosis in children. Clinically, it presents as well defined, yellowish papules that are typically located on the head, neck, upper trunk, and proximal region of the extremities. Although solitary lesions are the most common presentation, few cases of multiple juvenile xanthogranuloma have been described, more frequently associated with extracutaneous involvement. We report a 2-month-old girl with 22 cutaneous papules, clinically and histologically compatible with juvenile xanthogranulomas. Screening of visceral involvement was performed with no evidence of systemic disease. Identifying high-risk factors of systemic disease in patients with multiple juvenile xanthogranuloma is essential to perform an appropriate management of this entity.

Juvenile xanthogranuloma manifesting with LCH-associated neurodegenerative disease-like radiological findings.

Here, we describe two patients with juvenile xanthogranuloma (JXG) manifesting with Langerhans cell histiocytosis (LCH)-associated neurodegenerative disease (ND)-like radiological findings. One patient showed typical radiological abnormalities at onset, which worsened with progressing central nervous system symptoms 7 years after LCH-oriented chemotherapy. Another showed spontaneous regression of clinical symptoms, with a transient radiological change 1 year after salvage chemotherapy for recurrence of JXG. These data regarding JXG-associated ND will facilitate future investigation of the disease, as well as development of therapeutic interventions.

Congenital Juvenile Xanthogranuloma in the Perioral Region: A Case Image.

Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytosis in childhood. It often presents with cutaneous involvement and exhibits a predilection for the head and neck region. This article illustrates a case of congenital JXG in a 5-month-old boy, characterized by a solitary, well-circumscribed nodule above the left upper lip. Histopathologically, the lesion exhibited histiocytes with eosinophilic cytoplasm and Touton giant cells. Immunohistochemistry revealed histiocytes positive for CD68 and Factor XIIIa, while negative for S-100 protein. Clinicians should become familiar with the broad clinical spectrum of cutaneous JXG, particularly its congenital presentation, in order to ensure timely and accurate management.

Clinicopathological study of ophthalmic cutaneous and mucocutaneous non-langerhans cell histiocytic lesions.

BACKGROUND: The "C group" of the histiocytic disorders is characterized by non-Langerhans-cell histiocytic lesions in the skin, mucosal surfaces, or both, out of which Juvenile xanthogranuloma (JXG) is the most common typically affecting the skin. The eye is the most common extra-cutaneous site of JXG., we aim at providing our clinical and histopathological experience with this group of diseases including the adult-onset xanthogranuloma (AXG). METHODS: This is a retrospective cohort study of all patients with the tissue diagnosis of ocular and periocular cutaneous and mucocutaneous non-LCH disorders who presented to us over a period of 25 years (January 1993 to December 2018). RESULTS: Twenty patients were diagnosed as "Group C" disease with an age range of 2 months-60.9 years. Eleven patients were females (55%) and nine were males (45%). The involvement was mostly unilateral in 80.9%. All cases fell into the xanthogranuloma family with 11 JXG patients, 8 AXG patients of skin and ocular surface, and one patient with solitary reticulohistiocytoma (SRH). The clinical site of involvement in JXG was primarily in the eyelid in 5 patients (45%), ocular surface lesions in 2 (18%), iris in 2 (18%), choroidal and bilateral orbital lesions in 1 patient each (9%). The group of AXG, presented equally with eyelid lesions in 4/8 and ocular surface lesions in 4/8. The non-Langerhans' histiocytic infiltrate showed supportive immunohistochemical staining properties (reactive to CD68 marker and negative to S-100 and langerin markers). CONCLUSION: Among the rare histiocytic disorders, xanthogranulomatosis is the commonest and has wide clinical manifestations. Accurate diagnosis needs to be supported by typical histopathological findings. JXG was the commonest in our study with relatively older mean age at presentation and frequent eyelid rather than iris involvement. AXG is often confused with xanthelasma when involving the eyelids with corneal limbal involvement is relatively frequent.

Systemic xanthogranuloma involving bone marrow and skin in a case of B-Lymphoblastic Leukemia.

Juvenile xanthogranuloma is a benign self-limiting lesion commonly described in infants and young children. It most commonly involves the skin presenting as single or multiple yellowish-brown papules. Clinical scenario with the classic histomorphology showing histiocytic aggregates in the dermis with xanthomatous cytoplasm, toutan type giant cells, immunohistochemistry with positive CD68, CD163, factor XIIIa and negative CD1a and S-100 help in diagnosis. However, diagnosis becomes challenging with predominant systemic bone marrow involvement in post-B-lymphoblastic leukemia settings.

Histopathological maturation in juvenile xanthogranuloma: a blueberry muffin infant mimicking aleukemic leukemia cutis.

Juvenile xanthogranuloma (JXG) is usually identified by Touton giant cells, so their absence can complicate diagnosis. We encountered a case of non-typical neonatal JXG lacking Touton giant cells, which was difficult to differentiate from aleukemic leukemia cutis because of overlapping histopathological characteristics. A 1 month-old girl presented with a blueberry muffin rash and multiple 1-2 cm nodules within the subcutaneous and deeper soft tissues. Blood tests revealed pancytopenia. The initial nodule biopsy showed mononuclear cell infiltration, suggestive of mature monocytes or histiocytes, but no Touton giant cells. Bone marrow examination showed no evidence of leukemia. Despite worsening of the rash, pancytopenia, and weight gain over the following month, the results of the second biopsy remained consistent with the initial findings. Consequently, we provisionally diagnosed aleukemic leukemia cutis and initiated chemotherapy. After two courses of chemotherapy, the pancytopenia improved, but the nodules only partially regressed. A third biopsy of the nodule was performed to evaluate the histological response, and revealed Touton giant cells, confirming the diagnosis of JXG. In conclusion, distinguishing non-typical JXG from aleukemic leukemia cutis is challenging. This case highlights the importance of multiple biopsies and the potential for histopathological maturation.

[Giant and ulcerated juvenile xanthogranuloma: an atypical presentation in infants]. / Xantogranuloma juvenil gigante y ulcerado: una presentación atípica en lactantes.

Giant Juvenile Xanthogranuloma (GJXG) corresponds to an infrequent variant of Juvenile Xantho- granuloma (JXG) and is characterized by a lesion larger than 2 cm in diameter. It usually presents as a plaque but infrequently, presents as an ulcerated nodule. OBJECTIVE: To report two cases of atypical presentation of GJXG, highlighting the importance of considering them in the differential diagnosis of large, ulcerated tumors in infants. CLINICAL CASES: Case 1: A 4-month-old healthy male infant presented with a rapid and progressive growing left inguinal nodule, present since 2 months of age. At physical examination he presented with a 2.6 cm indurated erythematous nodule with central ulceration. Histological study of an incisional biopsy was compatible with JXG. Ophthalmologic involvement was ruled out. Because of functional impairment and parents worry complete surgical removal was performed. The patient had favorable evolution without local recurrence at 4 years of follow-up. Case 2: A 6-month-old healthy male infant presented with a 2.4 cm scapular crusted nodule of rapid and progressive growth, present since birth. Histological study of an incisional biopsy confirmed JXG. Ophthalmologic involvement was ruled out. After 18 months of periodic clinical follow-up, there was a progressive reduction in size of the lesion. CONCLUSIONS: The cases presented highlight the importance of considering JXG in the differential diagnosis of large, ulcerated tumors in infants. When encountered to atypical JXG presentations, histologic studies help to confirm the diagnosis. Given the favorable prognosis of this diagnosis, periodic clinical follow-up is advised; in exceptional cases, surgical or ablative treatments may be considered.

Juvenile xanthogranuloma as a differential diagnosis for sellar and suprasellar lesions in child: Case report and review of literature.

Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. Its systemic form affects 4% of patients. Lesions in the Central Nervous System (CNS) occur in 2% of systemic cases. Sellar JXG should be one of the differential diagnoses for sellar lesions in young. This is a 15-year-old patient with non-specific headache, progressive visual loss and magnetic resonance imaging showing sellar lesion with suprasellar extension. The patient underwent microsurgery by pterional craniotomy with partial resection of the tumor. Pathology evidenced JXG. It progressively evolved with impairment of neuroendocrine functions, new lesions in different CNS locations and death two years after diagnosis. Sellar JXG without cutaneous manifestations is rare. There are no specific findings of the disease. Diagnosis requires additional tests, being defined by pathological analysis. Total resection presents a greater potential control comparing to partial resection. Even so, some patients may have progressive disease with poor clinical outcome.

Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.

The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAF gene and mitogen-activated protein kinase pathway. In the current study, a novel CLTC :: SYK fusion in 3 cases of a histopathologically distinct histiocytic neoplasm arising as solitary soft tissue lesions in children identified by next-generation sequencing and fluorescence in situ hybridization is described. Morphologically, all 3 neoplasms were composed of sheets of cells with round-oval nuclei and vacuolated eosinophilic cytoplasm but, in contrast to classic juvenile xanthogranuloma (JXG), Touton giant cells were absent. A separate cohort of classic JXG cases subsequently profiled by fluorescence in situ hybridization were negative for the presence of a CLTC::SYK fusion suggesting that CLTC::SYK fusion-positive histiocytoma is genetically and histologically distinct from JXG. We postulate that the CLTC::SYK fusion leads to aberrant activation of the SYK kinase, which is involved in variable pathways, including mitogen-activated protein kinase. The identification of a novel CLTC::SYK fusion may pave the way for the development of targeted therapeutic options for aggressive disease.

Langerhans Cell Histiocytosis Evolving into Juvenile Xanthogranuloma: Two Linked Entities.

BACKGROUND: Langerhans cell histiocytosis (LCH) represents a myeloid clonal proliferation that involves the skin and other organs. Occasionally, cases of LCH evolve into juvenile xanthogranuloma (JXG). CASE PRESENTATION: A 7-month-old boy presented with an itchy, flaky rash resembling seborrheic dermatitis affecting the scalp and eyebrows. The lesions started at 2 months old. On physical examination, there were reddish/brown lesions on the trunk, denuded areas on the groin and neck, and a large lesion behind his bottom teeth. In addition, there were thick white plaques in his mouth and thick whitish material in both ears. A skin biopsy showed features of LCH. Radiologic examination demonstrated several osteolytic lesions. Chemotherapy produced marked improvement. A few months later, the patient developed lesions with clinical and histologic features of XG. CONCLUSION: A possible association between LCH and XG is explained by lineage maturation development. Chemotherapy may play a role in modifying the production of cytokines that enhance the transformation or 'maturation' of Langerhans cells into multinucleated macrophages (Touton cells) characteristic of a more favorable proliferative inflammatory condition.

Imaging features of juvenile xanthogranuloma.

BACKGROUND: Juvenile xanthogranuloma is rare in children and there are limited data on its imaging features. OBJECTIVE: To analyze the computed tomography (CT) and magnetic resonance imaging (MRI) features of juvenile xanthogranuloma in children. MATERIALS AND METHODS: A retrospective review was performed of clinical and radiographic data of histologically confirmed juvenile xanthogranuloma between January 2009 and June 2020. RESULTS: Fourteen children (4 girls, 10 boys; age range: 1 day to 13 years, mean age: 73 months) were included in the study: 4/14 had CT only, 5/14 had MRI only and 5/14 had CT and MRI. Sites of extracutaneous juvenile xanthogranuloma involvement included subcutaneous soft tissue (8/14), liver (2/14), lungs (2/14), kidney (2/14), nose (2/14), pancreas (1/14), central nervous system (1/14) and greater omentum (1/14), mainly manifested as single or multiple nodules or masses in different organs. On CT, the lesions mainly manifested as an iso-hypo density mass with mild or marked enhancement. On MRI, the lesions mainly manifested as slightly hyperintense on T1 and slightly hypointense on T2, with decreased diffusivity and homogeneous enhancement. Juvenile xanthogranuloma was not included in the imaging differential diagnosis in any case. CONCLUSION: Juvenile xanthogranuloma mainly manifests as single or multiple nodules or masses in different organs. Slight hyperintensity on T1 and slight hypointensity on T2 with decreased diffusivity and homogeneous enhancement are relatively characteristic imaging findings of juvenile xanthogranuloma. Combined with its typical skin lesions and imaging features, radiologists should include juvenile xanthogranuloma in the differential diagnosis when confronted with similar cases.

Oral Juvenile Xanthogranuloma: a case report of gingival hyperplasia and osteolysis in male adult patient.

BACKGROUND: Juvenile Xanthogranuloma (JXG) is a non-hereditary, self-limiting disease which is usually presented in infancy or early childhood and in males over females. CASE PRESENTATION: We report a rare case of oral Juvenile Xanthogranuloma with recurrent progressive gingival hyperplasia and concomitant presentation of osteolysis in a 21-year-old adult male with no significant medical history. Patient presented with generalized gingival hyperplasia, osteolysis of the maxilla and mandible, and a round, firm, nodular mass with clear circumference on the left shoulder. Results of gingival tissue biopsy, karyotype, bone marrow biopsy and immunohistochemistry were suggestive of a diagnosis of Juvenile Xanthogranuloma with no association to hematologic malignancy. Unfortunately, patient declined treatment and elected to be transferred back to local hospital for future evaluation. CONCLUSIONS: Juvenile Xanthogranuloma in adults can have atypical manifestations including generalized gingival hyperplasia and osteolysis of the maxilla and mandible. It should be differentiated between Langerhans cell histiocytosis, Papillon-Lefevre Syndrome, and Pyogenic Granulomas. Despite uncommon incidence, it should be included in differential diagnoses in cases of similar clinical presentations.

What is the Role of Different Macrophage Subsets in the Evolution of Juvenile Xanthogranulomas?

There are several activated forms of macrophages: 2 main groups are designated M1 and M2. While M1 macrophages have proinflammatory, bactericidal, and phagocytic functions and are the dominant phenotype observed in the early stages of inflammation, M2 macrophages are involved in constructive processes such as tissue repair; they play a role in wound healing and are required for revascularization and re-epithelialization. Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis. Its pathogenesis is not well understood, but it is not considered a neoplastic entity. JXGs possibly appear as a reaction to a nonspecific injury such as trauma or viral infection, although a genetic predisposition has been suggested in some cases. Tissue damage leads to a histiocytic response. JXGs appear, evolve toward maturation, and then most of them spontaneously regress. Young JXGs are characterized by small macrophages scattered in the dermis, in apposition close to the epidermis. As the lesion matures, the number of foamy macrophages and Touton cells increases and other cell types such as plasma cells, lymphocytes, and polymorphs are observed. Regressing xanthogranulomas will show numerous spindle cells in Significant values are in bold.a storiform distribution, interstitial fibrosis, and few foamy and Touton cells. In this study, we studied the immunophenotypic profile of macrophages found in cutaneous JXGs according to their stage of maturation. We examined the skin biopsies from 25 patients; all were embedded in paraffin and stained with hematoxylin and eosin and for immunohistochemistry. Typically, all JXGs were positive for factor XIIIa and CD4, and were negative for CD1a. The following histiocyte markers were used: CD68, CD204, CD163, MAC387, and HAM56. Images were analyzed by Image J software; data were statistically evaluated by SAS 9.0 software. The cases showed a slight predominance of males and the preference of the JXGs for the axial skin. Lesions occupied the papillary and reticular dermis in 85% of the cases and extended to the subcutaneous fat in the remainder. Compared with mature and regressing JXGs, younger lesions had a higher density of M1 macrophages, stained with MAC387. This antibody labels the histiocytes that have recently arrived in the areas of inflammation. As the lesions matured, there was an overwhelming predominance of M2 macrophages. These cells tended to cluster against the epidermis, except in the 2 cases in phase of regression. This suggests that there is a cross-talk between the epidermis and macrophages and that receptors, cytokines, chemokines, and adhesion molecules may play a role in the development and evolution of JXGs. These results indicate that, for most of their life, JXGs are formed by repairing M2 macrophages and are not just an M1 macrophagic response to a local antigen. The process appears to be influenced by chemical-mediator epidermal-macrophage cross-talking, considering the tendency of these cells to accumulate against the dermoepidermal junction.

Giant Juvenile Xanthogranuloma of face in an adult: A rare complexity.

Juvenile xanthogranuloma, a form of non-Langerhans cell histiocytosis can be defined as the proliferation of cells with macrophage like characteristics. It has been described as a benign, asymptomatic and common self-healing disorder of non-Langerhans cell histiocytosis (LCH), affecting mostly infants, children and rarely adults. We have documented a case of a 40 year old male who presented to us with extensive insidious papulonodulous growth over the face. The facial disfigurement caused was catastrophic. An extensive surgical excision and reconstruction was performed followed by histopathological evaluation. Microscopic study and immune histochemistry revaled Juvenile Xanthogranuloma of adult. The article highlights the presentation, diagnosis and management of this mammoth, rare disease.